Epitope-coated polymer particles elicit neutralising antibodies against Plasmodium falciparum sporozoites
Details
Publication Year 2021-11-29, Volume 6, Issue #1, Page 141
Journal Title
NPJ vaccines
Abstract
The current Malaria RTS,S vaccine is based on virus-like particles (VLPs) comprising the NANP repetitive epitopes from the cicumsporozoite protein (CSP) of Plasmodium falciparum. This vaccine has limited efficacy, only preventing severe disease in about 30% of vaccinated individuals. A more efficacious vaccine is urgently needed to combat malaria. Here we developed a particulate malaria vaccine based on the same CSP epitopes but using biopolymer particles (BPs) as an antigen carrier system. Specific B- and T-cell epitope-coated BPs were assembled in vivo inside an engineered endotoxin-free mutant of Escherichia coli. A high-yield production process leading to ~27% BP vaccine weight over biomass was established. The epitope-coated BPs were purified and their composition, i.e., the polymer core and epitope identity, was confirmed. Epitope-coated BPs were used alongside soluble peptide epitopes and empty BPs to vaccinate sheep. Epitope-coated BPs showed enhanced immunogenicity by inducing anti-NANP antibody titre of EC50 > 150,000 that were at least 20 times higher than induced by the soluble peptides. We concluded that the additional T-cell epitope was not required as it did not enhance immunogenicity when compared with the B-cell epitope-coated BPs. Antibodies specifically bound to the surface of Plasmodium falciparum sporozoites and efficiently inhibited sporozoite motility and traversal of human hepatocytes. This study demonstrated the utility of biologically self-assembled epitope-coated BPs as an epitope carrier for inclusion in next-generation malaria vaccines.
Publisher
NPG
WEHI Research Division(s)
Infectious Diseases And Immune Defence; Population Health And Immunity
PubMed ID
34845267
Open Access at Publisher's Site
https://doi.org/10.1038/s41541-021-00408-2
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2021-12-07 12:03:58
Last Modified: 2021-12-07 12:17:59
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